Chiral THP rings are ubiquitous substructures in natural and medicinally active products. Examples of the latter include aminoglycoside antibiotics (Umezawa, S. Adv. Carbohydr. Chem. Biochem. 1974, 30, 111-82), antimalarial agents (O'Neill, P. M., et al. J. Med. Chem. 2001, 44, 1467-70), selective ion-channel blockers for the treatment of heart disease (Yoo, S.-e. et al. J. Med. Chem. 2001, 44, 4207-15; Gerlach, U. et al. J. Med. Chem. 2001, 44, 3831-37), macrolide antibiotics and antitumor agents (Lee, E. et al. Bioorg. Med. Chem. Lett. 2002, 12, 3519-20), antidepressants (Maier, C. A.; Wunsch, B. J. Med. Chem. 2002, 45, 4923-30), and HIV protease inhibitors (Duffy, J. L. et al. Bioorg. Med. Chem. Lett. 2002, 12, 2423-26). Other applications include noncalorific sweeteners (Shallenberger, R. S.; Acree, T. E.; Lee, C. Y. Nature 1969, 221, 555-56. Levin, G. V. U.S. Pat. No. 4,262,032, 1981), pesticides (Levin, G. V.; Zehner, L. R. U.S. Pat. No. 5,166,193, 1992), ligands and auxiliaries for asymmetric synthesis and/or catalysis, ionophores, and optically active materials.
Many enantiopure THPs are carbohydrates or can be derived from carbohydrate precursors. One important consideration in this regard is the availability of D- and L-sugars, designated as such by the configuration of the chiral carbon most remote from the aldehydo/keto functionality (McNaught, A. D. Pur. Appl. Chem. 1996, 68, 1919-2008). L-sugars are often rare or unnatural products, but are known to have excellent potential as medicinal agents in their pyranosidic forms. For example, L-sugars are important constituents in antibiotics and other clinically useful agents such as heparin (Heparin—Chemical and Biological Properties; Clinical Applications. Lane, D. A.; Lindahl, U., eds. Edward Arnold: London, 1989). Known processes for making L-pyranosides include: (1) de novo syntheses (as illustrated in Ko, S. Y. et al. Science 1983, 220, 949-51), (2) homologation of shorter-chain sugars (as illustrated in Sowden, J. C. et al. J. Am. Chem. Soc. 1945, 67, 1713-15), and (3) epimerization of readily available D-sugars (as illustrated in Blanc-Muesser, M. et al, Synthesis 1977, 568-69). Methods for epimerizing D-sugars into L-sugars typically employ an acyclic intermediate to establish the L stereocenter, which often leads to a diastereomeric mixture of products upon cyclization. Several groups have reported epimerization of the critical stereocenter without opening the pyranose ring (as illustrated in Pegram, J. J.; et al., Carbohydr. Res. 1988, 184, 276-78); however, these routes have not demonstrated significant advantages in terms of synthetic efficiency or generality.
One method of synthesizing enantiopure THPs has been to transform common pyranosides such as D-glucose or D-galactose into DHPs known as D-glycals, in which the C1 and C2 substituents have been replaced with a double bond (enumerated positions used herein are based on the starting carbohydrate in accordance with standard nomenclature, see structure 1 below). Glycals have been widely used as synthetic intermediates in a variety of biologically active products, illustrating the value of such molecules (as illustrated in Tolstikov, A. G. et al., Russ. Chem. Rev. 1993, 62, 579). However, the D-glycal of structure 1 and related derivatives are limited in synthetic scope because certain substituents cannot be easily manipulated, particularly the C5 hydroxymethyl unit. This group defines the configuration of the carbohydrate (D or L) and is generally considered a permanent structural element on the ether ring. Moreover, access to L-glycals is severely limited by the poor availability of the corresponding L-sugars.

There is a continuing need for new and improved methods for synthesizing enantiopure DHPs and THPs from readily available chiral materials such as carbohydrates. In addition, there is a need for an efficient process for converting common D-pyranosides into natural or unnatural L-glycals and L-pyranosides without the aforementioned problems attendant to known techniques. 4-Deoxypentenosides (4-DPs), such as the compound of structure 2, are similar in appearance to glycals but possess a double bond on the other side of the pyranose ring. This structure, which was first reported in 1973 by Zemlicka and co-workers (Philips, K. D.; Zemlicka, J.; Horwitz, J. P. Carbohydr. Res. 1973, 30, 281-86), can be expected to have a similar reactivity profile to glycals with subsequent utility in organic synthesis. Compounds resulting from the synthetic application of 4-DPs and related DHPs are anticipated to be useful as medicinally active agents and other value-added products.